1. Technical Field
The present invention relates to the field of heart failure treatments. More specifically, the present invention relates to the use of transplanting cell populations, specifically stem cells, for the treatment of heart failure.
2. Description of the Related Art
Diseases of the cardiovascular system are a leading worldwide cause of mortality and morbidity. Heart failure has been increasing in prevalence. Heart failure is characterized by an inability of the heart to deliver sufficient blood to the various organs of the body. Current estimates indicate that over 5 million Americans carry the diagnosis of heart failure with nearly 500,000 new cases diagnosed each year and 250,000 deaths per year attributed to this disease. Despite significant therapeutic accomplishments in the past two decades, heart failure continues to increase in incidence reaching epidemic proportions and presenting a major economic burden in developed countries.
Heart failure is a clinical syndrome characterized by distinctive symptoms and signs resulting from disturbances in cardiac output or from increased venous pressure. Moreover, heart failure is a progressive disorder whereby the function of the heart continues to deteriorate over time despite the absence of adverse events. The result of heart failure is inadequate cardiac output.
Generally, there are two types of heart failure. Right heart failure is the inability of the right side of the heart to pump venous blood into pulmonary circulation. Thus, a back-up of fluid in the body occurs and results in swelling and edema. Left heart failure is the inability of the left side of the heart to pump blood into systemic circulation. Back-up behind the left ventricle then causes accumulation of fluid in the lungs.
The main resulting effect of heart failure is fluid congestion. If the heart becomes less efficient as a pump, the body attempts to compensate for it by using hormones and neural signals to increase blood volume.
Heart failure has numerous causes. For example, disease of heart tissue results in myocardial cells that no longer function. Thus, progression of left ventricular dysfunction has been attributed, in part, to ongoing loss of these cardiomyocytes.
There have been numerous methods of treating and preventing heart failure. For example, stem cells have been used to regenerate cardiac cells in acute cardiac ischemia and/or infarction or injury in animal models. In one particular example, viable marrow stromal cells isolated from donor leg bones were culture-expanded, labeled, and then injected into the myocardium of isogenic adult rat recipients. After harvesting the hearts from 4 days to 12 weeks after implantation, the implantation sites were examined and it was found that implanted stromal cells show the growth potential in a myocardial environment (Wang, et. al.).
Cardiomyocytes also have been shown to differentiate in vitro from pluripotent embryonic stem (ES) cells of line D3. The cells differentiated via embryo-like aggregates (embryoid bodies) that were characterized by the whole-cell patch-clamp technique, morphology, and gene expression analogy during the entire differentiation period (Maltsev, et. al., 1994). However, the cells must be differentiated in vitro prior to administration. Additionally, pluripotent mouse ES cells were able to differentiate, in vitro, into cardiomyocytes expressing major features of mammalian heart (Maltsev, et. al., 1993).
Stem cells, regardless of their origin (embryonic, bone marrow, skeletal muscle, etc), have the potential to differentiate into various, if not all, cell types of the body. Stem cells are able to differentiate into functional cardiac myocytes. Thus, the development of stem cell-based therapies for treating heart failure has many advantages over existing therapies.
There is a need for a method of improving and/or restoring cardiac function in patients with heart failure through the use of cardiac transplantation of stem cells. Additionally, there is a need for a method of increasing the performance of the heart through implantation and population of failing myocardium with stem cells.